Related Experiment Video
Updated: Jun 7, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Evaluation of cytarabine against Ewing sarcoma xenografts by the pediatric preclinical testing program
Peter J Houghton1, Christopher L Morton, Min Kang
1Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. peter.houghton@stjude.org
Abstract:
Treatment with the nucleoside analog cytarabine has been shown to mimic changes in gene expression associated with downregulation of the EWS-FLI1 oncogene in Ewing sarcoma cell lines, selectively inhibit their growth in vitro, and cause tumor regression in athymic nude mice. For this report cytarabine was studied in vitro against a panel of 23 pediatric cancer cell lines and in vivo against 6 Ewing sarcoma xenografts. Acute lymphoblastic leukemia cell lines were the most sensitive to cytarabine in vitro (median IC(50) 9 nM), while Ewing sarcoma cell lines showed intermediate sensitivity (median IC(50) 232 nM). Cytarabine at a dose of 150 mg/kg administered daily 5× failed to significantly inhibit growth of five xenograft models, but reduced growth rate of the A673 xenograft by 50%. Cytarabine shows no differential in vitro activity against Ewing sarcoma cell lines and is ineffective in vivo against Ewing sarcoma xenografts at the dose and schedule studied.
Insights
Cytarabine (cytidine arabinoside) showed limited effectiveness against Ewing sarcoma. While it inhibited some pediatric cancer cell lines, it was largely ineffective in vivo against Ewing sarcoma xenografts at the tested dose.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- The nucleoside analog cytarabine mimics gene expression changes related to EWS-FLI1 oncogene downregulation.
- Cytarabine selectively inhibits Ewing sarcoma cell growth in vitro and has shown tumor regression in animal models.
Purpose of the Study:
- To evaluate the in vitro and in vivo efficacy of cytarabine against pediatric cancer cell lines and Ewing sarcoma xenografts.
- To determine the sensitivity of various pediatric cancer types to cytarabine treatment.
Main Methods:
- In vitro testing of cytarabine against 23 pediatric cancer cell lines.
- In vivo testing of cytarabine against 6 Ewing sarcoma xenografts using a dose of 150 mg/kg daily for 5 days.
- Assessment of cell line sensitivity via IC50 values and xenograft growth inhibition.
Main Results:
- Acute lymphoblastic leukemia cell lines exhibited the highest sensitivity to cytarabine in vitro (median IC50 9 nM).
- Ewing sarcoma cell lines showed intermediate sensitivity in vitro (median IC50 232 nM).
- Cytarabine failed to significantly inhibit 5 out of 6 Ewing sarcoma xenografts; however, it reduced the growth rate of the A673 xenograft by 50%.
Conclusions:
- Cytarabine does not demonstrate differential in vitro activity against Ewing sarcoma cell lines.
- At the tested dose and schedule, cytarabine is ineffective in vivo against Ewing sarcoma xenografts.
